HMG-CoA reductase inhibitors (statins) as anticancer drugs (review). 2005

Gerhard Fritz
Department of Toxicology, University of Mainz, D-55131 Mainz, Germany. fritz@uni-mainz.de

Apart from their lipid lowering activity, HMG-CoA reductase inhibitors (statins) impair numerous cellular functions associated with metastasis, e.g. gene expression, angiogenesis, cell adhesion, cell motility and invasiveness. Furthermore, statins have impact on apoptotic cell death and modulate cellular susceptibility to cell killing by anticancer drugs and ionizing radiation. Part of the effects provoked by statins are due to the inhibition of the prenylation of low molecular weight GTPases, in particular Ras and Rho, which play key roles in signaling evoked by stimulation of cell surface receptors. C-terminal lipid modification of Ras/Rho GTPases is essential for their correct intracellular localization and function. By depletion of the cellular pool of isoprene precursor molecules, statins reduce the level of membrane-bound active Ras/Rho proteins, thereby impairing corresponding functions. Since broad clinical experience already exists for statins, their incorporation into established tumor-therapeutic regimens would be realizable in a rather short period of time. Here, data available at present arguing for the usefulness of statins in anticancer therapy are summarized and discussed.

UI MeSH Term Description Entries
D009362 Neoplasm Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Metastase,Metastasis,Metastases, Neoplasm,Metastasis, Neoplasm,Neoplasm Metastases,Metastases
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D011839 Radiation, Ionizing ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays. Ionizing Radiation,Ionizing Radiations,Radiations, Ionizing
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016923 Cell Death The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. Death, Cell
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D019161 Hydroxymethylglutaryl-CoA Reductase Inhibitors Compounds that inhibit HYDROXYMETHYLGLUTARYL COA REDUCTASES. They have been shown to directly lower CHOLESTEROL synthesis. HMG-CoA Reductase Inhibitor,HMG-CoA Reductase Inhibitors,Hydroxymethylglutaryl-CoA Reductase Inhibitor,Statin,Statins, HMG-CoA,Inhibitors, HMG-CoA Reductase,Inhibitors, Hydroxymethylglutaryl-CoA,Inhibitors, Hydroxymethylglutaryl-Coenzyme A,Statins,HMG CoA Reductase Inhibitor,HMG CoA Reductase Inhibitors,HMG-CoA Statins,Hydroxymethylglutaryl CoA Reductase Inhibitor,Hydroxymethylglutaryl CoA Reductase Inhibitors,Hydroxymethylglutaryl-CoA Inhibitors,Hydroxymethylglutaryl-Coenzyme A Inhibitors,Inhibitors, HMG CoA Reductase,Inhibitors, Hydroxymethylglutaryl CoA,Inhibitors, Hydroxymethylglutaryl Coenzyme A,Inhibitors, Hydroxymethylglutaryl-CoA Reductase,Reductase Inhibitor, Hydroxymethylglutaryl-CoA,Reductase Inhibitors, HMG-CoA,Reductase Inhibitors, Hydroxymethylglutaryl-CoA,Statins, HMG CoA
D020703 ras GTPase-Activating Proteins PROTEINS that specifically activate the GTP-phosphohydrolase activity of RAS PROTEINS. ras-GAPs,ras-GAP,GTPase-Activating Proteins, ras,ras GAP,ras GAPs,ras GTPase Activating Proteins
D020741 rho GTP-Binding Proteins A large family of MONOMERIC GTP-BINDING PROTEINS that are involved in regulation of actin organization, gene expression and cell cycle progression. This enzyme was formerly listed as EC 3.6.1.47. rho G-Proteins,rho GTPase,rho GTPases,rho Small GTP-Binding Proteins,P21 (rho)Protein,rho GTP-Binding Protein,rho Protein P21,G-Proteins, rho,GTP-Binding Protein, rho,GTP-Binding Proteins, rho,GTPase, rho,GTPases, rho,P21, rho Protein,rho G Proteins,rho GTP Binding Protein,rho GTP Binding Proteins,rho Small GTP Binding Proteins

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